Desolvation and Solvation-Substitution Theory
In an attempt to explain the high catalytic rates of enzymes, M.J.S. Dewar developed a different rationale [120].
18 This so-called ‘desolvation theory’ assumes that
the kinetics of enzyme reactions have much in common with those of gas-phase
reactions. Hence, if a substrate enters the active site of the enzyme, it replaces all of
the water molecules at the active site and a formal gas-phase reaction can take place
which mimics two reaction partners interacting without a ‘disturbing’ solvent. In
solution, the water molecules impede the approach of the partners, hence the
reaction rate is reduced. This theory would, inter alia, explain why small substrate
molecules are often slower converted than larger analogues, since the former are
unable to replace all the water molecules at the active site.
The ‘desolvation’ theory has recently been extended by a ‘solvation-substitution’
theory [122]. It is based on the assumption that the enzyme cannot strip off the water
surrounding the substrate to effect a ‘desolvation’, because this would be energetically unfavorable. Instead, the solvent is displaced by the environment of the active
site thereby affecting ‘solvation substitution’. Thus, the (often) hydrophobic substrate replaces the water with the (often) hydrophobic site of the enzyme which
favors the formation of the enzyme-substrate complex. In addition, the replacement
of water molecules within the active site during the substrate-approach decreases the
dielectric constant within this area, which in turn enhances electrostatic enzymesubstrate interactions. The latter cause proper substrate-orientation thereby leading
to an enhancement of catalytically productive events. This phenomenon is denoted
as ‘electrostatic catalysis’ and was coined as ‘Circe-effect’ by W. P. Jencks.
Entropy Effects
A major reason for the exceptional catalytic efficiency of enzymes over small
(chemical) catalysts is derived from the difference in size: The average (monomeric) protein used in biotransformations has a molecular weight of ~60,000 Da
and a diameter of ~50 Å, while a typical chemical homogeneous catalyst weights
~600 Da and measures ~10 Å across. This allows the enzyme to enclose its
substrate completely, with the catalytically active groups being positioned in
Induced Fit
Active Enzyme
Substrate
Enzyme
No Induced Fit
Inactive Enzyme
Substrate
Enzyme
X
A
X
X
X
B
A
Fig. 1.3 Schematic representation of the ‘induced-fit’ mechanism
18 A ‘record’ of rate acceleration factor of 10
14 has been reported. See [121].
1.4 Enzyme Properties and Nomenclature
15
In an attempt to explain the high catalytic rates of enzymes, M.J.S. Dewar developed a different rationale [120].
18 This so-called ‘desolvation theory’ assumes that
the kinetics of enzyme reactions have much in common with those of gas-phase
reactions. Hence, if a substrate enters the active site of the enzyme, it replaces all of
the water molecules at the active site and a formal gas-phase reaction can take place
which mimics two reaction partners interacting without a ‘disturbing’ solvent. In
solution, the water molecules impede the approach of the partners, hence the
reaction rate is reduced. This theory would, inter alia, explain why small substrate
molecules are often slower converted than larger analogues, since the former are
unable to replace all the water molecules at the active site.
The ‘desolvation’ theory has recently been extended by a ‘solvation-substitution’
theory [122]. It is based on the assumption that the enzyme cannot strip off the water
surrounding the substrate to effect a ‘desolvation’, because this would be energetically unfavorable. Instead, the solvent is displaced by the environment of the active
site thereby affecting ‘solvation substitution’. Thus, the (often) hydrophobic substrate replaces the water with the (often) hydrophobic site of the enzyme which
favors the formation of the enzyme-substrate complex. In addition, the replacement
of water molecules within the active site during the substrate-approach decreases the
dielectric constant within this area, which in turn enhances electrostatic enzymesubstrate interactions. The latter cause proper substrate-orientation thereby leading
to an enhancement of catalytically productive events. This phenomenon is denoted
as ‘electrostatic catalysis’ and was coined as ‘Circe-effect’ by W. P. Jencks.
Entropy Effects
A major reason for the exceptional catalytic efficiency of enzymes over small
(chemical) catalysts is derived from the difference in size: The average (monomeric) protein used in biotransformations has a molecular weight of ~60,000 Da
and a diameter of ~50 Å, while a typical chemical homogeneous catalyst weights
~600 Da and measures ~10 Å across. This allows the enzyme to enclose its
substrate completely, with the catalytically active groups being positioned in
Induced Fit
Active Enzyme
Substrate
Enzyme
No Induced Fit
Inactive Enzyme
Substrate
Enzyme
X
A
X
X
X
B
A
Fig. 1.3 Schematic representation of the ‘induced-fit’ mechanism
18 A ‘record’ of rate acceleration factor of 10
14 has been reported. See [121].
1.4 Enzyme Properties and Nomenclature
15